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Prothrombin factor complex

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https://www.readbyqxmd.com/read/28815410/efficacy-and-safety-of-a-4-factor-prothrombin-complex-concentrate-for-rapid-vitamin-k-antagonist-reversal-in-japanese-patients-presenting-with-major-bleeding-or-requiring-urgent-surgical-or-invasive-procedures-a-prospective-open-label-single-arm-phase-3b-study
#1
Shigeki Kushimoto, Toshio Fukuoka, Akio Kimura, Kazunori Toyoda, Andres Brainsky, Amy Harman, Thomas Chung, Masahiro Yasaka
Rapid vitamin K antagonist (VKA) reversal is required in patients experiencing major bleeding or requiring urgent surgery. Four-factor prothrombin complex concentrate (4F-PCC; Beriplex(®)/Kcentra(®)) was shown in two large randomized controlled, international phase 3b trials to be an effective alternative to plasma for urgent VKA reversal. In the present prospective, open-label, single-arm phase 3b trial, we evaluate the efficacy and safety of 4F-PCC in Japanese patients. Eleven patients [international normalized ratio (INR) ≥2] requiring rapid VKA reversal owing to major bleeding (n = 6) or before urgent surgical/invasive procedures (n = 5) were administered 4F-PCC dosed based on INR and weight...
August 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28804823/an-overview-of-thrombophilia-and-associated-laboratory-testing
#2
Martina Montagnana, Giuseppe Lippi, Elisa Danese
Venous thromboembolism, usually entailing deep vein thrombosis, pulmonary embolism, or both, is a complex and multifactorial disorder, in which a number of putative conditions interplay and finally contribute to propel the individual risk over a certain degree, so ultimately culminating in the development of venous occlusive disorders. Thrombophilia is commonly defined as a propensity to develop venous thromboembolism on the basis of an underlying hypercoagulable state attributable to inherited or acquired disorders of blood coagulation or fibrinolysis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28803708/anti-phospholipid-syndrome-current-opinion-on-mechanisms-involved-laboratory-characterization-and-diagnostic-aspects
#3
REVIEW
Jean Amiral, Marie Peyrafitte, Claire Dunois, Anne Marie Vissac, Jerard Seghatchian
Anti-phospholipid syndrome is a complex and severe clinical situation, associated with symptoms such as recurrent thrombosis, arterial or venous, at any site, pregnancy loss, and other related syndromes. These clinical burdens, are highly variable from patient to patient, and are associated with biological abnormalities, such as the presence of the Lupus Anticoagulant or phospholipid dependent antibodies, confirmed on two occasions at least 12 weeks apart. From the diagnosis standpoint, both, functional (clotting) or immunological assays, are difficult to standardize and to optimize, due to the absence of reference material, or a characteristic clinical group, and international reference preparations...
July 15, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28796276/colistin-dampens-fibrinolysis-and-endothelial-activation-during-endotoxaemia-a-randomised-double-blind-trial
#4
Christian Schoergenhofer, Peter Matzneller, Marion Mußbacher, Johannes A Schmid, Petra Jilma-Stohlawetz, Markus Zeitlinger, Bernd Jilma
Colistin electrostatically interacts with lipopolysaccharides (LPS). Pre-clinical studies demonstrated beneficial effects of colistin on LPS-induced coagulation and fibrinolysis. The objective of this trial was to investigate the effects of colistin during experimental endotoxaemia. In this randomised, double-blind, placebo-controlled, crossover trial 16 healthy volunteers received a 2 ng/kg LPS bolus after infusion of 2.5 million IU colistin or placebo. Plasma levels of F1+2 prothrombin fragments, thrombin-antithrombin complexes (TAT), von Willebrand factor antigen levels (vWF), E-selectin, plasmin-antiplasmin complexes (PAP), tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor-1 (PAI-1) were measured...
August 10, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28789610/management-of-refractory-bleeding-post-cardiopulmonary-bypass-in-an-acute-heparin-induced-thrombocytopenia-type-ii-renal-failure-patient-who-underwent-urgent-cardiac-surgery-with-bivalirudin-angiox-%C3%A2-anticoagulation
#5
Kimberly Hassen, Maria R Maccaroni, Haytham Sabry, Smitangshu Mukherjee, Shankari Serumadar, Inderpaul Birdi
Acute heparin-induced thrombocytopenia (HIT) patients present myriad anticoagulation management challenges in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy...
August 1, 2017: Perfusion
https://www.readbyqxmd.com/read/28769570/reversal-of-direct-oral-anticoagulants
#6
REVIEW
Mosaad Almegren
Reversal agents for direct oral anticoagulants (DOACs), including factor X inhibitors and direct thrombin inhibitors, are a major concern in clinical practice. After DOACs were introduced and became widely used as an alternative for vitamin K antagonists in the management of venous thromboembolism and nonvalvular atrial fibrillation, the need for effective reversal agents has increased, particularly for life-threatening bleeding episodes related to DOACs or to reverse medication effects during urgent interventions...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28765353/hemostatic-management-of-trauma-induced-coagulopathy
#7
Janise B Phillips, Phillip L Mohorn, Rebecca E Bookstaver, Tanya O Ezekiel, Christopher M Watson
Trauma-induced coagulopathy is a primary factor in many trauma-related fatalities. Management hinges upon rapid diagnosis of coagulation abnormalities and immediate administration of appropriate hemostatic agents. Use of crystalloids and packed red blood cells has traditionally been the core of trauma resuscitation, but current massive transfusion protocols include combination therapy with fresh frozen plasma and predefined ratios of platelets to packed red blood cells, limiting crystalloid administration. Hemostatic agents such as tranexamic acid, prothrombin complex concentrate, fibrinogen concentrate, and, in cases of refractory bleeding, recombinant activated factor VIIa may also be warranted...
August 2017: Critical Care Nurse
https://www.readbyqxmd.com/read/28763307/comparison-of-3-factor-versus-4-factor-prothrombin-complex-concentrate-with-regard-to-warfarin-reversal-blood-product-use-and-costs
#8
Jessica DeAngelo, Daniel Jarrell, Richard Cosgrove, James Camamo, Christopher Edwards, Asad E Patanwala
BACKGROUND: Prothrombin complex concentrates (PCCs) are drug products containing varying amounts of vitamin K-dependent coagulation factors II, VII, IX, and X. The evidence comparing 3-factor PCC (3-PCC) versus 4-factor PCC (4-PCC) for warfarin reversal is conflicting. It has been hypothesized that 3-PCC may be less effective than 4-PCC because of relatively lower factor VII content. STUDY QUESTION: The primary objective of this study was to compare international normalized ratio (INR) reversal between 3-PCC and 4-factor PCC (4-PCC) in warfarin-treated patients...
July 26, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28700408/three-versus-four-factor-prothrombin-complex-concentrates-for-factor-based-resuscitation-in-a-porcine-hemorrhagic-shock-model
#9
Donald Michael Moe, Michael Scott Lallemand, John Mason McClellan, Joshua Porter Smith, Shannon T Marko, Matthew J Eckert, Matthew J Martin
BACKGROUND: Bleeding is a leading cause of preventable death following severe injury. Prothrombin complex concentrates (PCC) treat inborn coagulation disorders and reverse oral anticoagulants, but are proposed for use in "factor-based" resuscitation strategies. Few studies exist for this indication in acidosis, or that compare 3-factor (3PCC) versus 4-factor (4PCC) products. We aimed to assess and compare their safety and efficacy in a porcine model of severe hemorrhagic shock and coagulopathy...
July 12, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28698333/research-protocol-for-platelets-in-out-of-hospital-cardiac-arrest-an-observational-case-controlled-feasibility-study-to-assess-coagulation-and-platelet-function-abnormalities-with-rotem-following-out-of-hospital-cardiac-arrest-pohcar
#10
Agnieszka Skorko, Matthew Thomas, Andrew Mumford, Thomas Johnson, Elinor Griffiths, Rosemary Greenwood, Jonathan Benger
INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) has an annual incidence of approximately 60 000 in the UK. Less than 10% of those who receive resuscitation survive to hospital discharge. For OHCA of a presumed cardiac cause, the optimal antiplatelet therapy is currently unknown. Previous studies indicate that a procoagulopathic state exists postcardiac arrest which may contribute to the formation of thrombi and contribute to poor outcomes. However, the administration of antiplatelet therapies needs to be balanced against the increased risk of bleeding that these individuals face...
July 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28691557/emicizumab-prophylaxis-in-hemophilia-a-with-inhibitors
#11
Johannes Oldenburg, Johnny N Mahlangu, Benjamin Kim, Christophe Schmitt, Michael U Callaghan, Guy Young, Elena Santagostino, Rebecca Kruse-Jarres, Claude Negrier, Craig Kessler, Nancy Valente, Elina Asikanius, Gallia G Levy, Jerzy Windyga, Midori Shima
Background Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. Methods We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B)...
July 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28684918/genotype-and-phenotype-correlation-in-intracranial-hemorrhage-in-neonatal-factor-vii-deficiency-among-thai-children
#12
Chanchai Traivaree, Chalinee Monsereenusorn, Arunotai Meekaewkunchorn, Premsak Laoyookhong, Saranya Suwansingh, Boonchai Boonyawat
Congenital factor VII (FVII) deficiency is a rare inherited coagulopathy. The clinical manifestations and clinical findings vary widely, ranging from asymptomatic to life-threatening bleeding, including intracranial hemorrhage (ICH), with prolonged prothrombin time, normal partial thromboplastin time and normal platelet counts, which are confirmed by the low level of FVII assay. Treatment consists of fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), and recombinant activated FVII to treat bleeding and prophylactic therapy...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28684417/noncanonical-proteolytic-activation-of-human-prothrombin-by-subtilisin-from-bacillus-subtilis-may-shift-the-procoagulant-anticoagulant-equilibrium-toward-thrombosis
#13
Giulia Pontarollo, Laura Acquasaliente, Daniele Peterle, Ilaria Artusi, Vincenzo De Filippis
Blood coagulation is a finely regulated physiological process culminating with the factor Xa (FXa)-mediated conversion of the prothrombin (ProT) zymogen to active αthrombin (αT). In the prothrombinase complex on the platelet surface, FXa cleaves ProT at Arg271, generating the inactive precursor prethrombin-2 (Pre2), which is further attacked at Arg320-Ile321 to yield mature αT. Whereas the mechanism of physiological ProT activation has been elucidated in great detail, little is known about the role of bacterial proteases, possibly released in the bloodstream during infection, in inducing blood coagulation by direct proteolytic ProT activation...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28683994/the-effects-of-steroids-on-coagulation-dysfunction-induced-by-cardiopulmonary-bypass-a-steroids-in-cardiac-surgery-sirs-trial-substudy
#14
Domenico Paparella, Alessandro Parolari, Crescenzia Rotunno, Jessica Vincent, Veronica Myasoedova, Pietro Guida, Micaela De Palo, Vito Margari, Philip J Devereaux, Andre Lamy, Francesco Alamanni, Salim Yusuf, Richard Whitlock
Cardiopulmonary bypass (CPB) surgery, despite heparin administration, elicits activation of coagulation system resulting in coagulopathy. Anti-inflammatory effects of steroid treatment have been demonstrated, but its effects on coagulation system are unknown. The primary objective of this study is to assess the effects of methylprednisolone on coagulation function by evaluating thrombin generation, fibrinolysis, and platelet activation in high-risk patients undergoing cardiac surgery with CPB. The Steroids In caRdiac Surgery study is a double-blind, randomized, controlled trial performed on 7507 patients worldwide who were randomized to receive either intravenous methylprednisolone, 250 mg at anesthetic induction and 250 mg at initiation of CPB (n = 3755), or placebo (n = 3752)...
April 2017: Seminars in Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28671348/novel-insights-into-the-regulation-of-coagulation-by-factor-v-isoforms-tissue-factor-pathway-inhibitor%C3%AE-and-protein-s
#15
B Dahlbäck
Factor V (FV) is a regulator of both pro- and anticoagulant pathways. It circulates as a single-chain procofactor, which is activated by thrombin or FXa to FVa that serves as cofactor for FXa in prothrombin activation. The cofactor function of FVa is regulated by activated protein C (APC) and protein S. FV can also function as an anticoagulant APC cofactor in the inhibition of FVIIIa in the membrane-bound tenase complex (FIXa/FVIIIa). In recent years, it has become clear that FV also functions in multiple ways in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway...
July 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28660341/low-dose-prothrombin-complex-concentrate-for-warfarin-associated-intracranial-hemorrhage-with-inr-less-than-2-0
#16
Wesley R Zemrak, Kathryn E Smith, Stephen S Rolfe, Teresa May, Robert L Trowbridge, Timothy L Hayes, Gene A Grindlinger, David B Seder
BACKGROUND: Prothrombin complex concentrates (PCCs) have become the first-line therapy for warfarin reversal in the setting of central nervous system (CNS) hemorrhage. Randomized, controlled studies comparing agents for warfarin reversal excluded patients with international normalized ratio (INR) <2, yet INR values of 1.6-1.9 are also associated with poor outcomes. METHODS: We retrospectively reviewed our use of a low-dose (15 units/kg) strategy of 4-factor PCC (4F-PCC) on warfarin reversal (INR 1...
June 28, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28654426/use-of-three-procoagulants-in-improving-bleeding-outcomes-in-the-warfarin-patient-with-intracranial-hemorrhage
#17
Emma P DeLoughery, Thomas G DeLoughery
: When patients on anticoagulation present with intracranial bleeding, stopping the bleeding is paramount. Despite the availability of multiple options to reverse anticoagulation, no study has directly compared the effectiveness of the procoagulants recombinant activated factor VII (rFVIIa), the rFVIIa and 3-factor prothrombin complex concentrate (PCC) combination, and 4-factor PCC on improving patient outcomes compared with a control. This study examined the medical records of 197 warfarin patients with intracranial hemorrhage, an initial international normalized ratio (INR) greater than 1...
June 24, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28635130/prothrombin-complex-concentrate-for-emergent-reversal-of-warfarin-an-international-survey-of-hospital-protocols
#18
J Gorlin, S Kinney, M K Fung, A Tinmouth
For emergent warfarin reversal, four-factor prothrombin complex concentrates (4FPCCs) are recommended by many international guidelines. We surveyed international clinical sites including members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Most sites have emergent warfarin reversal protocols (53% use PCC, 25% use PCC+ plasma and 2% use plasma alone); however, variation between adjusted dosing and fixed dosing was observed.
June 21, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28612131/three-factor-versus-four-factor-prothrombin-complex-concentrate-for-the-emergent-management-of-warfarin-associated-intracranial-hemorrhage
#19
Daniel Fischer, Jeffrey Sorensen, Gabriel V Fontaine
BACKGROUND: Four-factor prothrombin complex concentrates (PCC) produce a more rapid and complete INR correction compared with 3-factor PCC in patients receiving warfarin. It is unknown if this improves clinical outcomes in the setting of intracranial hemorrhage (ICH). METHODS: This multicenter, retrospective cohort study included patients presenting with warfarin-associated ICH reversed with either 4- or 3-factor PCC. The primary outcome was in-hospital mortality...
June 13, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28604569/use-of-four-factor-prothrombin-complex-concentrate-in-the-reversal-of-warfarin-induced-and-nonvitamin-k-antagonist-related-coagulopathy
#20
Hannah Young, Jeremy L Holzmacher, Richard Amdur, Stephen Gondek, Babak Sarani, Mary E Schroeder
: To evaluate the efficacy of international normalized ratio (INR) reversal using four-factor prothrombin complex concentrate (4F-PCC) in nonmedication-induced coagulopathy. We performed a single-site, retrospective cohort study of patients receiving off-label use of 4F-PCC. Cohorts included liver dysfunction if they had acute liver decompensation or cirrhosis without other causative factors of liver failure such as sepsis, coagulopathy of acute sepsis (CAS) if they had documentation of sepsis and no underlying liver disorder, known factor deficiencies, or medication-induced coagulopathy, or warfarin if they were taking warfarin...
June 9, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
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